Population Distribution, Settlement Patterns and Accessibility across Africa in 2010

The spatial distribution of populations and settlements across a country and their interconnectivity and accessibility from urban areas are important for delivering healthcare, distributing resources and economic development. However, existing spatially explicit population data across Africa are generally based on outdated, low resolution input demographic data, and provide insufficient detail to quantify rural settlement patterns and, thus, accurately measure population concentration and accessibility. Here we outline approaches to developing a new high resolution population distribution dataset for Africa and analyse rural accessibility to population centers. Contemporary population count data were combined with detailed satellite-derived settlement extents to map population distributions across Africa at a finer spatial resolution than ever before. Substantial heterogeneity in settlement patterns, population concentration and spatial accessibility to major population centres is exhibited across the continent. In Africa, 90% of the population is concentrated in less than 21% of the land surface and the average per-person travel time to settlements of more than 50,000 inhabitants is around 3.5 hours, with Central and East Africa displaying the longest average travel times. The analyses highlight large inequities in access, the isolation of many rural populations and the challenges that exist between countries and regions in providing access to services. The datasets presented are freely available as part of the AfriPop project, providing an evidence base for guiding strategic decisions

Meta-analysis of genome-wide association studies of asthma in ethnically diverse North American populations.

Asthma is a common disease with a complex risk architecture including both genetic and environmental factors. We performed a meta-analysis of North American genome-wide association studies of asthma in 5,416 individuals with asthma (cases) including individuals of European American, African American or African Caribbean, and Latino ancestry, with replication in an additional 12,649 individuals from the same ethnic groups. We identified five susceptibility loci. Four were at previously reported loci on 17q21, near IL1RL1, TSLP and IL33, but we report for the first time, to our knowledge, that these loci are associated with asthma risk in three ethnic groups. In addition, we identified a new asthma susceptibility locus at PYHIN1, with the association being specific to individuals of African descent (P = 3.9 × 10(-9)). These results suggest that some asthma susceptibility loci are robust to differences in ancestry when sufficiently large samples sizes are investigated, and that ancestry-specific associations also contribute to the complex genetic architecture of asthma

Spatiotemporal patterns of population in mainland China, 1990 to 2010

According to UN forecasts, global population will increase to over 8 billion by 2025, with much of this anticipated population growth expected in urban areas. In China, the scale of urbanization has, and continues to be, unprecedented in terms of magnitude and rate of change. Since the late 1970s, the percentage of Chinese living in urban areas increased from ~18% to over 50%. To quantify these patterns spatially we use time-invariant or temporally-explicit data, including census data for 1990, 2000, and 2010 in an ensemble prediction model. Resulting multi-temporal, gridded population datasets are unique in terms of granularity and extent, providing fine-scale (~100 m) patterns of population distribution for mainland China. For consistency purposes, the Tibet Autonomous Region, Taiwan, and the islands in the South China Sea were excluded. The statistical model and considerations for temporally comparable maps are described, along with the resulting datasets. Final, mainland China population maps for 1990, 2000, and 2010 are freely available as products from the WorldPop Project website and the WorldPop Dataverse Repository

Suppression of PP2A is critical for protection of melanoma cells upon endoplasmic reticulum stress

Endoplasmic reticulum (ER) stress triggers apoptosis by activating Bim in diverse types of cells, which involves dephosphorylation of BimEL by protein phosphatase 2A (PP2A). However, melanoma cells are largely resistant to ER stress-induced apoptosis, suggesting that Bim activation is suppressed in melanoma cells undergoing ER stress. We show here that ER stress reduces PP2A activity leading to increased ERK activation and subsequent phosphorylation and proteasomal degradation of BimEL. Despite sustained upregulation of Bim at the transcriptional level, the BimEL protein expression was downregulated after an initial increase in melanoma cells subjected to pharmacological ER stress. This was mediated by increased activity of ERK, whereas the phosphatase activity of PP2A was reduced by ER stress in melanoma cells. The increase in ERK activation was, at least in part, due to reduced dephosphorylation by PP2A, which was associated with downregulation of the PP2A catalytic C subunit. Notably, instead of direct dephosphorylation of BimEL, PP2A inhibited its phosphorylation indirectly through dephosphorylation of ERK in melanoma cells. Taken together, these results identify downregualtion of PP2A activity as an important protective mechanism of melanoma cells against ER stress-induced apoptosis

CRP identifies homeostatic immune oscillations in cancer patients: a potential treatment targeting tool?

The search for a suitable biomarker which indicates immune system responses in cancer patients has been long and arduous, but a widely known biomarker has emerged as a potential candidate for this purpose. C-Reactive Protein (CRP) is an acute-phase plasma protein that can be used as a marker for activation of the immune system. The short plasma half-life and relatively robust and reliable response to inflammation, make CRP an ideal candidate marker for inflammation. The high- sensitivity test for CRP, termed Low-Reactive Protein (LRP, L-CRP or hs-CRP), measures very low levels of CRP more accurately, and is even more reliable than standard CRP for this purpose. Usually, static sampling of CRP has been used for clinical studies and these can predict disease presence or recurrence, notably for a number of cancers. We have used frequent serial L-CRP measurements across three clinical laboratories in two countries and for different advanced cancers, and have demonstrated similar, repeatable observations of a cyclical variation in CRP levels in these patients. We hypothesise that these L-CRP oscillations are part of a homeostatic immune response to advanced malignancy and have some preliminary data linking the timing of therapy to treatment success. This article reviews CRP, shows some of our data and advances the reasoning for the hypothesis that explains the CRP cycles in terms of homeostatic immune regulatory cycles. This knowledge might also open the way for improved timing of treatment(s) for improved clinical efficacy

Striatal sensitivity to personal responsibility in a regret-based decision-making task

Regret and relief are complex emotional states associated with the counterfactual processing of nonobtained outcomes in a decision-making situation. In the "actor effect," a sense of agency and personal responsibility is thought to heighten these emotions. Using fMRI, we scanned volunteers (n = 22) as they played a task involving choices between two wheel-of-fortune gambles. We examined how neural responses to counterfactual outcomes were modulated by giving subjects the opportunity to change their minds, as a manipulation of personal responsibility. Satisfaction ratings to the outcomes were highly sensitive to the difference between the obtained and nonobtained outcome, and ratings following losses were lower on trials with the opportunity to change one's mind. Outcome-related activity in the striatum and orbitofrontal cortex was positively related to the satisfaction ratings. The striatal response was modulated by the agency manipulation: Following losses, the striatal signal was significantly lower when the subject had the opportunity to change his/her mind. These results support the involvement of frontostriatal mechanisms in counterfactual thinking and highlight the sensitivity of the striatum to the effects of personal responsibility.</p

Equity Ownership Strategy in Greenfield Investments : Influences of Host Country Infrastructure and MNE Resources in Emerging Markets

This chapter addresses equity ownership strategy in greenfield investments by multinational enterprises (MNEs) in the emerging markets (EMs). It is one of the few studies to hypothesize and analyze influences of host EM physical infrastructure in relation to investment decisions of MNEs. We use resource dependence theory (RDT) as a theoretical basis and test the moderating effects of firm resources like size and host country investment experience. Moreover, the current study assumes a more nuanced approach to studying equity ownership by analyzing wholly owned subsidiaries versus joint ventures (JVs) and including majority versus minority JVs in the analysis as well. The empirical results based on greenfield investments undertaken by Nordic (Danish, Finnish, Norwegian, and Swedish) MNEs in EMs during 1990–2015 reveals the importance of host country physical infrastructure for high equity ownership strategy. Moreover, host country investment experience moderates the effect of physical infrastructure on equity ownership strategy. Finally, the analysis of a sub-sample of greenfield JVs reveals that determinants of equity ownership strategy differ somewhat between greenfield JV or greenfield wholly owned subsidiaries (WOS).© The Author(s) 2019.fi=vertaisarvioitu|en=peerReviewed

Association of IL-4RA single nucleotide polymorphisms, HLA-DR and HLA-DQ in children with Alternaria-sensitive moderate-severe asthma

<p>Abstract</p> <p>Background</p> <p>Asthma afflicts 6% to 8% of the United States population, and severe asthma represents approximately 10% of asthmatic patients. Several epidemiologic studies in the United States and Europe have linked <it>Alternaria </it>sensitivity to both persistence and severity of asthma. In order to begin to understand genetic risk factors underlying <it>Alternaria </it>sensitivity and asthma, in these studies we examined T cell responses to <it>Alternaria </it>antigens, HLA Class II restriction and HLA-DQ protection in children with severe asthma.</p> <p>Methods</p> <p>Sixty children with <it>Alternaria</it>-sensitive moderate-severe asthma were compared to 49 children with <it>Alternaria</it>-sensitive mild asthma. We examined HLA-DR and HLA-DQ frequencies in <it>Alternaria</it>-sensitive asthmatic by HLA typing. To determine ratios of Th1/Th2 <it>Alternaria</it>-specific T-cells, cultures were stimulated in media alone, <it>Alternaria alternata </it>extract and Alt a1. Sensitivity to IL-4 stimulation was measured by up-regulation of CD23 on B cells.</p> <p>Results</p> <p>Children with <it>Alternaria</it>-sensitive moderate-severe asthma trended to have increased sensitivities to <it>Cladosporium </it>(46% versus 35%), to <it>Aspergillus </it>(43% versus 28%), and significantly increased sensitivities to trees (78% versus 57%) and to weeds (68% versus 48%). The IL-4RA ile75val polymorphism was significantly increased in <it>Alternaria</it>-sensitive moderate-severe asthmatics, 83% (0.627 allele frequency) compared to <it>Alternaria</it>-sensitive mild asthmatics, 57% (0.388 allele frequency). This was associated with increased sensitivity to IL-4 stimulation measured by significantly increased IL-4 stimulated CD23 expression on CD19+ and CD86+CD19+ B cells of <it>Alternaria</it>-sensitive moderate-severe asthmatics. IL-5 and IL-13 synthesis was significantly increased in <it>Alternaria</it>-sensitive moderate-severe asthmatics compared to mild asthmatics to <it>Alternaria </it>extract and Alt a1 stimulation. The frequency of HLA-DQB1*03 allele was significantly decreased in <it>Alternaria</it>-sensitive moderate-severe asthmatics compared to mild asthmatics, 39% versus 63%, with significantly decreased allele frequency, 0.220 versus 0.398.</p> <p>Summary</p> <p>In children with <it>Alternaria</it>-sensitive moderate severe asthma, there was an increased Th2 response to <it>Alternaria </it>stimulation and increased sensitivity to IL-4 stimulation. This skewing towards a Th2 response was associated with an increased frequency of the IL-4RA ile75val polymorphism. In evaluating the HLA association, there was a decreased frequency of HLA-DQB1*03 in <it>Alternaria</it>-sensitive moderate severe asthmatic children consistent with previous studies suggest that HLA-DQB1*03 may be protective against the development of mold-sensitive severe asthma.</p

Serologic and immunohistochemical prognostic biomarkers of cutaneous malignancies

Biomarkers are important tools in clinical diagnosis and prognostic classification of various cutaneous malignancies. Besides clinical and histopathological aspects (e.g. anatomic site and type of the primary tumour, tumour size and invasion depth, ulceration, vascular invasion), an increasing variety of molecular markers have been identified, providing the possibility of a more detailed diagnostic and prognostic subgrouping of tumour entities, up to even changing existing classification systems. Recently published gene expression or proteomic profiling data relate to new marker molecules involved in skin cancer pathogenesis, which may, after validation by suitable studies, represent future prognostic or predictive biomarkers in cutaneous malignancies. We, here, give an overview on currently known serologic and newer immunohistochemical biomarker molecules in the most common cutaneous malignancies, malignant melanoma, squamous cell carcinoma and cutaneous lymphoma, particularly emphasizing their prognostic and predictive significance